Genome 373: Genomic Informatics. Professors Elhanan Borenstein and Jay Shendure

Transkriptio

1 Genome 373: Genomic Informatics Professors Elhanan Borenstein and Jay Shendure

2 Genome 373 This course is intended to introduce students to the breadth of problems and methods in computational analysis of genomes, arguably the single most important new area in biological research. The specific subjects will include: Sequence alignment Sequencing and next generation sequencing Gene prediction Micro-array analysis Evolutionary relationships and phylogeny Biological systems

3 Outline Course logistics Introduction to Bioinformatics Introduction to Python

4 Instructors Elhanan Borenstein: Weeks 1-2, 8-10 Jay Shendure: Weeks 3-7 Office hours: Monday 11:20-12:00 Jacob Kitzman(TA) will teach additional topics including programming and problem solving skills. Material covered in section is required, and will be on the exams.

5 Webpage Web site: Page has links to Lecture notes Handouts Homework assignments Many useful resources on: Bioinformatics Python

6 Programming Note: Historically, this course required prior programming experience. The first couple of weeks in class and the first few weeks of section will focus on learning to program in Python. If you do not have any programming experience, that s ok, but you will need to work hard to catch up.

7 Grading 50% homework 20% midterm exam (in class) 30% final exam, Mon, June 4 Final exam is cumulative.

8 Homework Posted online each Wednesday and due the following Wednesday. Homework is a mix of written problems and programming. Homework assignments are to be submitted by ! Programming assignments should be implemented in Python. For other languages, please ask Jacob. More on home assignment submission in the quiz section.

9 Textbooks

10 Background survey Please write on the index card your: 1. Name and 2. Major 3. Primarybackground (biology, computation, other) 4. Programming experience (how much, what language) 5. Registered/not-registered/waiting-list

11 Why Bioinformatics?

12 tgcaagcatgcacatgtaccaggagaaaatgaagacaattgtggaaacttttagacttttcatcaactttctagtgtcacttttttgccgctttcct atctgatagttgcgaagactccgaagaaaatgagaatggtgaaggctagcatgctgatgcttcatttctctggagcaattgtggatttctatctaag cttcatttcgatcccagtgctcactttgcccgtttgctcaggtatccattgggattctcgttggtgttaggaattccaacgtctgttcaagtttata tcggagtttcatgtatgggcggtgggtcgctctgttgcaggaggtcttgaatttcttttttgcagtaatcggtgtaactattcttatatttttcgaa aatcgttactttcaactaatcaatggatcttctggtggtagaagttggaagcgaaaactatatgttttgtgtaattacgcgttctctgtaactttta tagctccagcgtttttagacatttttagtgaagaacaaggaagagcgtgcacgtttgaagtaagttaggcaaaccaaactcgctagtgtgatgaaat tttccagaaaattccgagtatccctatcgacgtgccttctcgctcaggatattttgtcctattaattgataacccagtctacagcatttgcgtaagc ctcttggtaattaaagtgtgcccacaaattggtatagtcgttttgttcatattcccttatattgttcaaacgaaatcacattctcgagccacacttc gtttacttcttcacttttttatcgcgatgtgtatccagctgtctattccatttttggtcatcttcttgccggctgcttttatagtgtacgcaattca atatgactattataatcaaggtatgaatattaggccttccacgaaggcgctattctcgcccgcccgtaccacaccaacgctcttctcagttgcacgc ggctatagtagcgcgagggcccgcgtagcgtcggccgccttcatagaaggtctaatgaatatatagtattaagtataatttaaataaagtttcagca gcaaacaacttggcgatggcaacaatggcattccatggggtatgtactacactgaccatgatcatcgtgcatacaccgtatcgtaacgctactttga gcattttacatctgaaatcggaaaaatcggcaaaaacagtgactgattcgaagattgtgtggaaaagtaacaagggagtacagatgacataaactat gcccattgttaccctatattttatttttctctatggtgacaactttatcttaagaaaaacacgcatataaatcaagcagttcctggtcacaggacgt ttacttccacctgtttctaatttcttataaaaccctatatctttcaagttttttccacaagactctgccactctgacacttatgtgctcgactagcc tcagcttctttgcttccgagcaaacatatataaaacttctacatactcttaccatacttgaactttccactcactcttttggagcatacatcatcat tacaaaaacaccgaaaaagttggaatccgtgaaggccagcatgctctatctacaatttgttggagcatttgtcgatgtctatttcagttggttagct atgccgattctagtactacctttatgtgcaggacatgcgattggcttactttcattttttggggttccaagctcgttgcaagtttatgtaggtttct gttcactagcaggttggttcttaagaatgatggagagcgtcacatgtattgtgttgtacagatacaatttgaaagcaatccaatacagcgtgtaaaa gttttgcaattataaacatcattgcagttatggttatgacagtagtgatctttctggaagatcgtcgatatcggttggtgaacggtcaaaagtcaaa caaaatgagaaaattgtatcggttactgtttgtcacagctaattatgtttatgctacattgtaccctgctcccatatactttttgcttcccgaccaa gaatatggaagaattttatcgaaaagtgtacgtcttaaaaagtttgaaacatatacaatgaaatgtcttacttttaaagtttgcgtttcagaaaaat ccgtgtattccgaacgaatatttaaaccatcctaatttctttttgcttgatctcgatggaaagtatacttcaatttgtatcctgcttatgttgagtt ctctggtctctcaaatgttttggcaaattggactgattttccgtcagatgctcaaaaatccgtccgtttctcaaaatacgcaccgactacaatacca gtttttaattgcaatgagcttgcaaggcaccattccaatgattatcattgtttttccagcttttttctatgttgtctcaattatgttaaattatcat aatcaaggtattgtatctattcggaacaagacattaaacataattccaacttttcaggtgcaaataacttatcgtttcttatcatttccatgcatgg agttctatcaacgttgacaatgctcatggcacacagaccgtatagacaatcgattgtcaaaatgttgaatctgaatttcaataaggcaggtggtggt gttcaacgtatttggacgctttccagaagaaataattaatgatgaccttggaaaaggctaatcttcacaacaatcaaatcaaataatcataaaagtt tttattgaagaaaaataaactatctgtgcacagaaatccaatgaattgctctatctacaatttgttggagcatttgtcgatgtctatttcagttggt tagctatgccgattctagtactacctttatgtgcaggacatgcgattggcttactttcattttttggggttccaagctcgttgcaagtttatgtagg tttctgttcactagcaggttggttcttaagaatgatggagagcgtcacatgtattgtgttgtacagatacaatttgaaagcaatccaatacagcgtg taaaagttttgcaattataaacatcattgcagttatggttatgacagtagtgatctttctggaagatcgtcgatatcggttggtgaacggtcaaaag Find the binding sequence: caattatgttaaa

13 tgcaagcatgcacatgtaccaggagaaaatgaagacaattgtggaaacttttagacttttcatcaactttctagtgtcacttttttgccgctttcct atctgatagttgcgaagactccgaagaaaatgagaatggtgaaggctagcatgctgatgcttcatttctctggagcaattgtggatttctatctaag cttcatttcgatcccagtgctcactttgcccgtttgctcaggtatccattgggattctcgttggtgttaggaattccaacgtctgttcaagtttata tcggagtttcatgtatgggcggtgggtcgctctgttgcaggaggtcttgaatttcttttttgcagtaatcggtgtaactattcttatatttttcgaa aatcgttactttcaactaatcaatggatcttctggtggtagaagttggaagcgaaaactatatgttttgtgtaattacgcgttctctgtaactttta tagctccagcgtttttagacatttttagtgaagaacaaggaagagcgtgcacgtttgaagtaagttaggcaaaccaaactcgctagtgtgatgaaat tttccagaaaattccgagtatccctatcgacgtgccttctcgctcaggatattttgtcctattaattgataacccagtctacagcatttgcgtaagc ctcttggtaattaaagtgtgcccacaaattggtatagtcgttttgttcatattcccttatattgttcaaacgaaatcacattctcgagccacacttc gtttacttcttcacttttttatcgcgatgtgtatccagctgtctattccatttttggtcatcttcttgccggctgcttttatagtgtacgcaattca atatgactattataatcaaggtatgaatattaggccttccacgaaggcgctattctcgcccgcccgtaccacaccaacgctcttctcagttgcacgc ggctatagtagcgcgagggcccgcgtagcgtcggccgccttcatagaaggtctaatgaatatatagtattaagtataatttaaataaagtttcagca gcaaacaacttggcgatggcaacaatggcattccatggggtatgtactacactgaccatgatcatcgtgcatacaccgtatcgtaacgctactttga gcattttacatctgaaatcggaaaaatcggcaaaaacagtgactgattcgaagattgtgtggaaaagtaacaagggagtacagatgacataaactat gcccattgttaccctatattttatttttctctatggtgacaactttatcttaagaaaaacacgcatataaatcaagcagttcctggtcacaggacgt ttacttccacctgtttctaatttcttataaaaccctatatctttcaagttttttccacaagactctgccactctgacacttatgtgctcgactagcc tcagcttctttgcttccgagcaaacatatataaaacttctacatactcttaccatacttgaactttccactcactcttttggagcatacatcatcat tacaaaaacaccgaaaaagttggaatccgtgaaggccagcatgctctatctacaatttgttggagcatttgtcgatgtctatttcagttggttagct atgccgattctagtactacctttatgtgcaggacatgcgattggcttactttcattttttggggttccaagctcgttgcaagtttatgtaggtttct gttcactagcaggttggttcttaagaatgatggagagcgtcacatgtattgtgttgtacagatacaatttgaaagcaatccaatacagcgtgtaaaa gttttgcaattataaacatcattgcagttatggttatgacagtagtgatctttctggaagatcgtcgatatcggttggtgaacggtcaaaagtcaaa caaaatgagaaaattgtatcggttactgtttgtcacagctaattatgtttatgctacattgtaccctgctcccatatactttttgcttcccgaccaa gaatatggaagaattttatcgaaaagtgtacgtcttaaaaagtttgaaacatatacaatgaaatgtcttacttttaaagtttgcgtttcagaaaaat ccgtgtattccgaacgaatatttaaaccatcctaatttctttttgcttgatctcgatggaaagtatacttcaatttgtatcctgcttatgttgagtt ctctggtctctcaaatgttttggcaaattggactgattttccgtcagatgctcaaaaatccgtccgtttctcaaaatacgcaccgactacaatacca gtttttaattgcaatgagcttgcaaggcaccattccaatgattatcattgtttttccagcttttttctatgttgtctcaattatgttaaattatcat aatcaaggtattgtatctattcggaacaagacattaaacataattccaacttttcaggtgcaaataacttatcgtttcttatcatttccatgcatgg agttctatcaacgttgacaatgctcatggcacacagaccgtatagacaatcgattgtcaaaatgttgaatctgaatttcaataaggcaggtggtggt gttcaacgtatttggacgctttccagaagaaataattaatgatgaccttggaaaaggctaatcttcacaacaatcaaatcaaataatcataaaagtt tttattgaagaaaaataaactatctgtgcacagaaatccaatgaattgctctatctacaatttgttggagcatttgtcgatgtctatttcagttggt tagctatgccgattctagtactacctttatgtgcaggacatgcgattggcttactttcattttttggggttccaagctcgttgcaagtttatgtagg tttctgttcactagcaggttggttcttaagaatgatggagagcgtcacatgtattgtgttgtacagatacaatttgaaagcaatccaatacagcgtg taaaagttttgcaattataaacatcattgcagttatggttatgacagtagtgatctttctggaagatcgtcgatatcggttggtgaacggtcaaaag Find the binding sequence: caattatgttaaa

14 Computer processing power doubles every ~2 years. Moore s law dotted line - 2 year doubling

15 Sequencing cost decreasing much fasterthan computing cost >2-fold drop per year? - changing so fast hard to be specific

16 Viruses Bacteria Archaea Fungi Animals Plants ~ Kb ~1-5 Mb ~1-5 Mb ~10-50 Mb ~100-5,000 Mb ~100-10,000 Mb As of 2011 done or nearly done > 2,000 viruses > 1,000 bacteria and archaea Hundreds of fungi Dozens of protists Dozens of nematodes and insects 6 fish, 1 reptile, 4 birds, 1 amphibian About 10 plants About 40 mammals (+multiple individuals) Microbial communities (e.g., human microbiome) ~3100 bases (3.1Kb)

17 A computational bottleneck

18 Find the binding sequence: caattatgttaaa allowing for one mutation and one insertion gaattatgttaaa catttatgttaaa caatt-atgttaaa cagttat-gttaaa cagttatgttaaa caattatgtta-aa caattatattaaa cagttatgttaa-a caattatgttaat caattatgt-taaa caattatgttaaa caaatatgttaaa caat-tatgttaaa ca-attatggtaaa caattatgttaaa c-aattatgttata caattatgttaga

19 How well can the string GAATTCAGTTA match the string GGATCGA? (what is the best alignment between the two strings?) G A A T T C A G T T A G G A T C G - - A

20 InformaticsChallenges: Examples Sequence comparison: Find the best match (alignment) of a given sequence in a large dataset of sequences Find the best alignment of two sequences Find the best alignment of multiple sequences Motif and gene finding Relationship between sequences Phylogeny Clustering and classification Many manymanymore

21